Quality by Design and Design Space Principles Clarified in ICH Q8 Annex

The International Conference on Harmonization has released an Annex to its Q8 guideline, Pharmaceutical Development. The annex provides further clarification of key concepts outlined in the core guideline. It describes the principles of quality by design (QbD), and shows how concepts and tools (e.g., design space) outlined in the Q8 document may be put into practice for all dosage forms.

The section on design space includes information on selecting variables; defining and describing a design space in a submission; and the relationship of design space to scale and equipment. The document also says that knowing where the edges of failure could be, although helpful, is not an essential part of establishing a design space.

A chart in Appendix 1 to the document illustrates the difference between “minimal” and “enhanced” approaches to various aspects of pharmaceutical development. For example, the chart contrasts the two approaches to a manufacturing process as follows:

Minimal approach:
• Fixed
• Validation primarily based on initial full-scale batches
• Focus on optimization and reproducibility

Enhanced approach:
• Adjustable within design space
• Lifecycle approach to validation and, ideally, continuous process verification
• Focus on control strategy and robustness
• Use of statistical process control methods

The guideline was released on November 1, 2007, under Step 2 of the ICH process.

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